An increasing number of progressive neurodegenerative diseases are now recognized to be caused by an expanded CAG trinucleotide repeat. These repeats encode polyglutamine tracts within the protein coding region of the gene. Machado-Joseph disease (MJD) is a member of the CAG triplet repeat fancy and recently the defective gene in MJD, MJD1, has been identified. Based on its predicted amino acid sequence it is expected to be an intracellular protein however its function remains unknown. I propose to use a variety of techniques to characterize the normal function of the MJD1 gene product and to identify how the expanded repeat form leads to neuronal death.